Sensory-evoked synaptic network discharges generated in the dorsal horn regions of fetal mouse spinal cord explants with attached dorsal root ganglia (DRGs) can be selectively depressed by exposure to analgesic concentrations of morphine, other opiates, and opioid peptides (Crain et al. Br. Res. 133, '77; 157, '78). These depressant effects are reversed by naloxone as in situ. High stereospecific opiate receptor binding levels have been demonstrated in these cultures, especially in the DRG neurites (Hiller et al. Br. Res. 145, '78). Enhancement of sensory-evoked cord responses by naloxone in cultures not previously exposed to exogenous opiates suggests that these dorsal horn networks may also develop opiate inhibitory control systems mediated by enkephalins. This new tissue culture model will be utilized to analyze some of the mechanisms underlying the physiologic effects of acute as well as chronic exposure to opiates and endorphins, including the role of calcium ions and cyclic AMP in opiate effects on CNS functions, and the development of tolerance and dependence. Cellular localization of opiate receptors and enkephalins in spinal cord-DRG explants and in cultures of isolated DRG or cord neurons will be correlated with functional analyses. Studies of opioid neural networks in cord-DRG explants will be extended to co-cultures with explants of monoaminergic brainstem tissues which may be involved in regulation of nociceptive opioid systems. Coordinated bioelectric and histofluorescence analyses of these monoaminergic pathways in culture may provide further insights into the development of the complex neural circuits regulating opioid networks of the spinal cord and brainstem. Similar techniques have been used in our studies of aminergic neurons in explants of locus coeruleus co-cultured with hippocampus (Dreyfus et al., Br. Res. 161, '79). Correlative studies of opioid and aminergic networks in vitro may clarify some of the cellular mechanisms linking these important neural control systems in situ.